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1.
Sci Total Environ ; : 176535, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332716

RESUMO

Soil reinforcement using eco-friendly biopolymer and vegetation has been increasingly popular in geotechnical engineering. However, research is still in its early stages due to complex biochemical interactions between biopolymers and plants. Moreover, under the increasing climate change, extreme weather poses severe challenges to the effectiveness of biopolymer-vegetation on soil treatment. Therefore, this paper provides a comprehensive review and summary of recent research on the influence of biopolymer and biopolymer-vegetation interaction on soil properties. First, this paper evaluates the various hydraulic and mechanical properties of soils after biopolymer treatment, including compaction characteristics, Atterberg limits, unconfined compressive strength, shear strength, tensile strength, permeability, water holding capacity, slaking behavior, and erosion resistance, as well as the influence of climate change. Then, the application of biopolymer-vegetation measure in the current field of soil treatment is summarized, and the biopolymer-vegetation interaction is discussed, including the influence of biopolymers on plant germination rate, growth conditions, wilting rate, and other indicators. Under drought and water scarcity conditions, biopolymers can improve soil mechanical strength and water retention, reducing plant wilting rate, and enhancing the survival ability of plants under extreme climate changes. Appropriate biopolymers can increase soil strength by >50 %, reduce strength and mass losses from dry-wet cycles to within 10 %, enhance grass seed germination rates by over 60 %, and reduce wilting rates under drought stress by 80 %. Finally, the research gaps and deficiencies in this field are highlighted, and potential research hotspots that can be strengthened and studied in the future are proposed. This review demonstrates the biopolymer-vegetation measure to be a new ecological restoration technology with widespread application prospects.

2.
Comput Methods Programs Biomed ; 257: 108428, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39326361

RESUMO

BACKGROUND: Cardioembolic strokes are commonly occurred in non-valvular atrial fibrillation (AF) patients, with over 90% of cases originating from clot in left atrial appendage (LAA), which is believed to be greatly related with hemodynamic characters. Numerical simulation is widely accepted in the hemodynamic analysis, and patient-specific boundaries are required for realistic numerical simulations. METHOD: This paper firstly proposed a method that maps personalized pulmonary venous flow (PVF) by utilizing the volume changes of the left atrium (LA) over the cardiac cycle. Then we used data from patients with AF to investigate the correlation between PVF patterns and hemodynamics within the LAA. Meanwhile, we conducted a fluid-structure interaction analysis to assess the impact of velocity- and time-related PVF parameters on LAA hemodynamic characters. RESULTS: The analysis reveal that the ratio of systolic to diastolic peak velocity (VS/VD), and systolic velocity-time integral (VTI) showed a significant influence on LAA velocity in patients with atrial fibrillation, and the increases of velocity- and time-related parameters were found to be positively correlated with the blood update in the LAA. CONCLUSIONS: This study established a method for mapping patient-specific PVF based on LA volume change, and evaluated the relationship between PVF parameters and thrombosis risk. The present work provides an insight from PVF characters to evaluate the risk of thrombus formation within LAA in patients with AF.

3.
Plant Biotechnol J ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276323

RESUMO

Vernalization and photoperiod pathways converging at FT1 control the transition to flowering in wheat. Here, we identified a gain-of-function mutation in FT-D1 that results in earlier heading date (HD), and shorter plant height and spike length in the gamma ray-induced eh1 wheat mutant. Knockout of the wild-type and overexpression of the mutated FT-D1 indicate that both alleles are functional to affect HD and plant height. Protein interaction assays demonstrated that the frameshift mutation in FT-D1eh1 exon 3 led to gain-of-function interactions with 14-3-3A and FDL6, thereby enabling the formation of florigen activation complex (FAC) and consequently activating a flowering-related transcriptomic programme. This mutation did not affect FT-D1eh1 interactions with TaNaKR5 or TaFTIP7, both of which could modulate HD, potentially via mediating FT-D1 translocation to the shoot apical meristem. Furthermore, the 'Segment B' external loop is essential for FT-D1 interaction with FDL6, while residue Y85 is required for interactions with TaNaKR5 and TaFTIP7. Finally, the flowering regulatory hub gene, ELF5, was identified as the FT-D1 regulatory target. This study illustrates FT-D1 function in determining wheat HD with a suite of interaction partners and provides genetic resources for tuning HD in elite wheat lines.

4.
Oncol Lett ; 28(5): 503, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39233824

RESUMO

Uveal melanoma (UM) is a highly metastatic cancer with resistance to immunotherapy. The present study aimed to identify novel feature genes and molecular mechanisms in UM through analysis of single-cell sequencing data. For this purpose, data were downloaded from The Cancer Genome Atlas and National Center for Biotechnology Information Gene Expression Omnibus public databases. The statistical analysis function of the CellPhoneDB software package was used to analyze the ligand-receptor relationships of the feature genes. The Metascape database was used to perform the functional annotation of notable gene sets. The randomForestSRC package and random survival forest algorithm were applied to screen feature genes. The CIBERSORT algorithm was used to analyze the RNA-sequencing data and infer the relative proportions of the 22 immune-infiltrating cell types. In vitro, small interfering RNAs were used to knockdown the expression of target genes in C918 cells. The migration capability and viability of these cells were then assessed by gap closure and Cell Counting Kit-8 assays. In total, 13 single-cell sample subtypes were clustered by t-distributed Stochastic Neighbor Embedding and annotated by the R package, SingleR, into 7 cell categories: Tissue stem cells, epithelial cells, fibroblasts, macrophages, natural killer cells, neurons and endothelial cells. The interactions in NK cells|Endothelial cells, Neurons|Endothelial cells, CD74_APP, and SPP1_PTGER4 were more significant than those in the other subsets. T-Box transcription factor 2, tropomyosin 4, plexin D1 (PLXND1), G protein subunit α I2 (GNAI2) and SEC14-like lipid binding 1 were identified as the feature genes in UM. These marker genes were found to be significantly enriched in pathways such as vasculature development, focal adhesion and cell adhesion molecule binding. Significant correlations were observed between key genes and immune cells as well as immune factors. Relationships were also observed between the expression levels of the key genes and multiple disease-related genes. Knockdown of PLXND1 and GNAI2 expression led to significantly lower viability and gap closure rates of C918 cells. Therefore, the results of the present study uncovered cell communication between endothelial cells and other cell types, identified innovative key genes and provided potential targets of gene therapy in UM.

5.
Clin Exp Pharmacol Physiol ; 51(10): e13921, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39223829

RESUMO

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial degeneration resulting in impaired visual acuity. Excessive deposition of extracellular matrix (guttae) on Descemet's membrane (DM) is the hallmark of FECD. We sought to detect the guttae area rapidly using aniline blue (AB) staining in FECD mouse model. FECD mouse model was established via ultraviolet A (UVA) exposure. Masson's trichrome staining was utilized to stain the corneal sections. AB staining was utilized to stain both whole cornea tissues and stripped Descemet's membrane-endothelium complex (DMEC) flat mounts, while immunofluorescence staining of collagen I was employed to stain guttae areas. In Masson's trichrome staining, corneal collagen fibrils were stained blue with AB. The DMEC flat mounts were stained into relative dark blue areas and relative light blue areas using 2% AB staining. The areas of dark blue could almost overlap with collagen I-positive areas, and have an acellular centre and a moderately distinct boundary line with the surrounding corneal endothelial cells. In conclusion, AB staining is a rapid and effective method for the evaluation of the guttae areas in the FECD mouse model.


Assuntos
Compostos de Anilina , Modelos Animais de Doenças , Distrofia Endotelial de Fuchs , Animais , Camundongos , Distrofia Endotelial de Fuchs/patologia , Distrofia Endotelial de Fuchs/metabolismo , Coloração e Rotulagem/métodos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Lâmina Limitante Posterior/patologia , Lâmina Limitante Posterior/metabolismo , Camundongos Endogâmicos C57BL , Endotélio Corneano/patologia , Endotélio Corneano/metabolismo , Corantes
6.
J Cell Mol Med ; 28(18): e70079, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39300613

RESUMO

This study aimed to identify feature genes and explore the molecular mechanisms of keratoconus (KC). We downloaded data files from NCBI GEO public database. The Limma package was used for differential expression analysis of gene profiles. Lasso regression was used to identify the feature genes. The CIBERSORT algorithm was used to infer the proportion of immune-infiltrating cells and analyse the correlation between gene expression levels and immune cells. Related transcription factors and miRNAs of key genes were predicted using the Cistrome DB and Mircode databases. Analysis of expression differences in disease genes was based on the GeneCards database. The CMap was used to analyse targeted therapeutic drugs. IHC was performed to verify the expression levels of ATOH7 and MYRF in corneas. Exactly 593 upregulated and 473 downregulated genes were identified. Lasso regression analysis identified ATOH7, DBNDD1, RNF217-AS1, ARL11, MYRF and SNORA74B as feature genes for KC. All key genes were correlated with immune infiltration and the levels of activated memory CD4+ T cells and plasma cells were significantly increased. miRNA, IRF and STAT families were correlated to feature genes. The expression levels of key genes were significantly correlated to KC-related genes. Entinostat, ochratoxin-a, diphencyprone and GSK-3-inhibitor-II were predicted as potential KC medications. The expression of MYRF was significantly higher in the KC samples, contrary to the expression of ATOH7. KC is related to both immune infiltration and genetic factors. MYRF and ATOH7 were newly identified and verified feature genes of KC.


Assuntos
Ceratocone , Ceratocone/genética , Ceratocone/metabolismo , Humanos , MicroRNAs/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Bases de Dados Genéticas , Transcriptoma/genética , Redes Reguladoras de Genes , Biologia Computacional/métodos
7.
Nat Commun ; 15(1): 7244, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39174532

RESUMO

The filamentous 'Pf' bacteriophages of Pseudomonas aeruginosa play roles in biofilm formation and virulence, but mechanisms governing Pf prophage activation in biofilms are unclear. Here, we identify a prophage regulatory module, KKP (kinase-kinase-phosphatase), that controls virion production of co-resident Pf prophages and mediates host defense against diverse lytic phages. KKP consists of Ser/Thr kinases PfkA and PfkB, and phosphatase PfpC. The kinases have multiple host targets, one of which is MvaU, a host nucleoid-binding protein and known prophage-silencing factor. Characterization of KKP deletion and overexpression strains with transcriptional, protein-level and prophage-based approaches indicates that shifts in the balance between kinase and phosphatase activities regulate phage production by controlling MvaU phosphorylation. In addition, KKP acts as a tripartite toxin-antitoxin system that provides defense against some lytic phages. A conserved lytic phage replication protein inhibits the KKP phosphatase PfpC, stimulating toxic kinase activity and blocking lytic phage production. Thus, KKP represents a phosphorylation-based mechanism for prophage regulation and antiphage defense. The conservation of KKP gene clusters in >1000 diverse temperate prophages suggests that integrated control of temperate and lytic phage infection by KKP-like regulatory modules may play a widespread role in shaping host cell physiology.


Assuntos
Lisogenia , Prófagos , Pseudomonas aeruginosa , Lisogenia/genética , Pseudomonas aeruginosa/virologia , Pseudomonas aeruginosa/genética , Prófagos/genética , Prófagos/fisiologia , Fosforilação , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Fagos de Pseudomonas/genética , Fagos de Pseudomonas/metabolismo , Biofilmes/crescimento & desenvolvimento , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Regulação Viral da Expressão Gênica
8.
Int J Nanomedicine ; 19: 8541-8553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185347

RESUMO

Background: Chemodynamic therapy (CDT) faces challenges of low catalytic ion efficiency and ROS production. We developed a ROS nano-bomb, Cu/ZIF-8@GA-Fe, to address these issues. Methods: The nano-bomb was synthesized by doping copper into ZIF-8 and assembling Fe3+ and gallic acid (GA). It was tested for reactive oxygen species (ROS) generation in acidic conditions and its photothermal properties. Results: In an acidic micro environment, Cu/ZIF-8@GA-Fe effectively released Fe3+ and Cu2+, depleting GSH and generating ROS. The GA-Fe coating provided photothermal heat and was used to enhance Fenton reactions via dual ions for increasing ROS production. In vivo and in vitro experiments, Cu/ZIF-8@GA-Fe inhibited tumor growth with minimal side effects. Conclusion: Cu/ZIF-8@GA-Fe shows promise for safe and effective CDT, offering a synergistic approach to tumor therapy.


Assuntos
Cobre , Ácido Gálico , Glutationa , Espécies Reativas de Oxigênio , Ácido Gálico/química , Ácido Gálico/farmacologia , Cobre/química , Cobre/farmacologia , Animais , Glutationa/química , Espécies Reativas de Oxigênio/metabolismo , Humanos , Camundongos , Linhagem Celular Tumoral , Terapia Fototérmica/métodos , Ferro/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos BALB C , Nanopartículas Metálicas/química , Terapia Combinada , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Cell Prolif ; : e13704, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961590

RESUMO

Dry eye disease (DED) is a growing public health concern affecting millions of people worldwide and causing ocular discomfort and visual disturbance. Developing its therapeutic drugs based on animal models suffer from interspecies differences and poor prediction of human trials. Here, we established long-term 3D human corneal epithelial organoids, which recapitulated the cell lineages and gene expression signature of the human corneal epithelium. Organoids can be regulated to differentiate ex vivo, but the addition of FGF10 inhibits this process. In the hyperosmolar-induced DED organoid model, the release of inflammatory factors increased, resulting in damage to the stemness of stem cells and a decrease in functional mucin 1 protein. Furthermore, we found that the organoids could mimic clinical drug treatment responses, suggesting that corneal epithelial organoids are promising candidates for establishing a drug testing platform ex vivo. In summary, we established a functional, long-term 3D human epithelial organoid that may serve as an ex vivo model for studying the functional regulation and disease modelling.

10.
Biology (Basel) ; 13(6)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38927310

RESUMO

The erect leaf plays a crucial role in determining plant architecture, with its growth and development regulated by genetic factors. However, there has been a lack of comprehensive studies on the regulatory mechanisms governing wheat lamina joint development, thus failing to meet current breeding demands. In this study, a wheat erect leaf mutant, mths29, induced via fast neutron mutagenesis, was utilized for QTL fine mapping and investigation of lamina joint development. Genetic analysis of segregating populations derived from mths29 and Jimai22 revealed that the erect leaf trait was controlled by a dominant single gene. Using BSR sequencing and map-based cloning techniques, the QTL responsible for the erect leaf trait was mapped to a 1.03 Mb physical region on chromosome 5A. Transcriptome analysis highlighted differential expression of genes associated with cell division and proliferation, as well as several crucial transcription factors and kinases implicated in lamina joint development, particularly in the boundary cells of the preligule zone in mths29. These findings establish a solid foundation for understanding lamina joint development and hold promise for potential improvements in wheat plant architecture.

12.
Biomater Adv ; 161: 213901, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776602

RESUMO

The permeability and the effective diffusivity of a porous scaffold are critical in the bone-ingrowth process. However, design guidelines for porous structures are still lacking due to inadequate understanding of the complex physiological processes involved. In this study, a model integrating the fundamental biological processes of bone regeneration was constructed to investigate the roles of permeability and effective diffusivity in regulating bone deposition in scaffolds. The in silico analysis results were confirmed in vivo by examining bone depositions in three diamond lattice scaffolds manufactured using selective laser melting. The findings show that the scaffolds with better permeability and effective diffusivity had deeper bone ingrowth and greater bone volume. Compared to permeability, effective diffusivity exhibited greater sensitivity to the orientation of porous structures, and bone ingrowth was deeper in the directions with higher effective diffusivity in spite of identical pore size. A 4.8-fold increase in permeability and a 1.6-fold increase in effective diffusivity by changing the porous structure led to a 1.5-fold increase in newly formed bone. The effective diffusivity of the porous scaffold affects the distribution of osteogenic growth factor, which in turn impacts cell migration and bone deposition through chemotaxis effects. Therefore, effective diffusivity may be a more suitable indicator for porous scaffolds because our study shows changes in this parameter determine changes in bone distribution and bone volume.


Assuntos
Regeneração Óssea , Osteogênese , Permeabilidade , Alicerces Teciduais , Alicerces Teciduais/química , Porosidade , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Animais , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Osso e Ossos , Simulação por Computador , Engenharia Tecidual/métodos
13.
Artigo em Inglês | MEDLINE | ID: mdl-38583228

RESUMO

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Ressonância de Plasmônio de Superfície , Trombose , Feminino , Humanos , Masculino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Imunoensaio/métodos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Ressonância de Plasmônio de Superfície/métodos , Trombose/sangue
14.
BMC Endocr Disord ; 24(1): 45, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622616

RESUMO

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.


Assuntos
Neoplasias Hipofisárias , Sinusite , Humanos , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Endoscopia/efeitos adversos , Cefaleia/etiologia , Cefaleia/prevenção & controle , Lavagem Nasal
15.
Mol Breed ; 44(2): 12, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38313680

RESUMO

Tiller number greatly contributes to grain yield in wheat. Using ethylmethanesulfonate mutagenesis, we previously discovered the oligo-tillering mutant ot1. The tiller number was significantly lower in ot1 than in the corresponding wild type from the early tillering stage until the heading stage. Compared to the wild type, the thousand-grain weight and grain length were increased by 15.41% and 31.44%, respectively, whereas the plant height and spike length were decreased by 26.13% and 37.25%, respectively. Transcriptomic analysis was conducted at the regreening and jointing stages to identify differential expressed genes (DEGs). Functional enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases showed differential expression of genes associated with ADP binding, transmembrane transport, and transcriptional regulation during tiller development. Differences in tiller number in ot1 led to the upregulation of genes in the strigolactone (SL) and abscisic acid (ABA) pathways. Specifically, the SL biosynthesis genes DWARF (D27), D17, D10, and MORE AXILLARY GROWTH 1 (MAX1) were upregulated by 3.37- to 8.23-fold; the SL signal transduction genes D14 and D53 were upregulated by 1.81- and 1.32-fold, respectively; the ABA biosynthesis genes 9-CIS-EPOXICAROTENOID DIOXIGENASE 3 (NCED3) and NCED5 were upregulated by 1.66- and 3.4-fold, respectively; and SNF1-REGULATED PROTEIN KINASE2 (SnRK2) and PROTEIN PHOSPHATASE 2C (PP2C) genes were upregulated by 1.30- to 4.79-fold. This suggested that the tiller number reduction in ot1 was due to alterations in plant hormone pathways. Genes known to promote tillering growth were upregulated, whereas those known to inhibit tillering growth were downregulated. For example, PIN-FORMED 9 (PIN9), which promotes tiller development, was upregulated by 8.23-fold in ot1; Ideal Plant Architecture 1 (IPA1), which inhibits tiller development, was downregulated by 1.74-fold. There were no significant differences in the expression levels of TILLER NUMBER 1 (TN1) or TEOSINTE BRANCHED 1 (TB1), indicating that the tiller reduction in ot1 was not controlled by known genes. Our findings provide valuable data for subsequent research into the genetic bases and regulatory mechanisms of wheat tillering. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01450-3.

16.
Exp Eye Res ; 241: 109832, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38369232

RESUMO

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of endothelial keratoplasty without efficacious drug treatment. Recent studies have emphasized the involvement of epigenetic regulation in FECD development. Long non-coding RNAs (lncRNAs) are recognized as crucial epigenetic regulators in diverse cellular processes and ocular diseases. In this study, we revealed the expression patterns of lncRNAs using high-throughput sequencing technology in FECD mouse model, and identified 979 significantly dysregulated lncRNAs. By comparing the data from FECD human cell model, we obtained a series of homologous lncRNAs with similar expression patterns, and revealed that these homologous lncRNAs were enriched in FECD related biological functions, with apoptosis (mmu04210) showing the highest enrichment score. In addition, we investigated the role of lncRNA zinc finger antisense 1 (ZFAS1) in apoptotic process. This study would broaden our understanding of epigenetic regulation in FECD development, and provide potential anti-apoptotic targets for FECD therapy.


Assuntos
Distrofia Endotelial de Fuchs , RNA Longo não Codificante , Animais , Humanos , Camundongos , Endotélio Corneano/metabolismo , Epigênese Genética , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , RNA Longo não Codificante/genética , Zinco/metabolismo
17.
Plant Physiol Biochem ; 207: 108425, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38368728

RESUMO

As climate change continues to negatively impact our farmlands, abiotic factors like salinity and drought stress increasingly threaten global food security. The development of elite germplasms with resistance to multiple abiotic stresses is essential for breeding climate-resilient wheat cultivars. In this study, we determined that the previously reported salt-tolerant st1 mutant, obtained via spaceflight mutagenesis, may also resist to drought stress at the seedling stage. Moreover, our field trial revealed that yield-related traits including plant height, 1000-grain weight, and spike number per plant were significantly increased in st1 compared to the wild type. An F2 population of 334 individuals derived from a cross between the wild type and st1 displayed a bimodal distribution indicating that st1 plant height is controlled by a single major gene. Our Bulked Segregant Analysis and exome capture sequencing indicate that this gene is located on chromosome 4D. Further genetic linkage and gene sequence analysis suggests that a reverse mutation of Rht2 is putatively responsible for plant height variation in st1. Our genotypic and phenotypic analysis of the F2 population and F3 lines indicate that this reverse mutation significantly increases plant height and thousand grain weight but slightly decreases spike number per plant. Together, these results supply helpful information for the utilization of Rht2 in wheat breeding and provide an important material for breeding environmentally resilient, high-yield wheat varieties.


Assuntos
Voo Espacial , Triticum , Humanos , Triticum/genética , Melhoramento Vegetal , Fenótipo , Mutação/genética , Grão Comestível
18.
Adv Healthc Mater ; 13(3): e2302409, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37964681

RESUMO

In recent years, messenger RNA (mRNA) vaccines have exhibited great potential to replace conventional vaccines owing to their low risk of insertional mutagenesis, safety and efficacy, rapid and scalable production, and low-cost manufacturing. With the great achievements of chemical modification and sequence optimization methods of mRNA, the key to the success of mRNA vaccines is strictly dependent on safe and efficient gene vectors. Among various delivery platforms, non-viral mRNA vectors could represent perfect choices for future clinical translation regarding their safety, sufficient packaging capability, low immunogenicity, and versatility. In this review, the recent progress in the development of non-viral mRNA vectors is focused on. Various organic vectors including lipid nanoparticles (LNPs), polymers, peptides, and exosomes for efficient mRNA delivery are presented and summarized. Furthermore, the latest advances in clinical trials of mRNA vaccines are described. Finally, the current challenges and future possibilities for the clinical translation of these promising mRNA vectors are also discussed.


Assuntos
Nanopartículas , Vacinas , Vacinas de mRNA , Vetores Genéticos , RNA Mensageiro/genética , Polímeros
19.
Nat Chem Biol ; 20(1): 42-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37563455

RESUMO

Protein lipidation, which regulates numerous biological pathways and plays crucial roles in the pharmaceutical industry, is not encoded by the genetic code but synthesized post-translationally. In the present study, we report a computational approach for designing lipidation mimics that fully recapitulate the biochemical properties of natural lipidation in membrane association and albumin binding. Furthermore, we establish an engineered system for co-translational incorporation of these lipidation mimics into virtually any desired position of proteins in Escherichia coli and mammalian cells. We demonstrate the utility of these length-tunable lipidation mimics in diverse applications, including improving the half-life and activity of therapeutic proteins in living mice, anchoring functional proteins to membrane by substituting natural lipidation, functionally characterizing proteins carrying different lengths of lipidation and determining the plasma membrane-binding capacity of a given compound. Our strategy enables gain-of-function studies of lipidation in hundreds of proteins and facilitates the creation of superior therapeutic candidates.


Assuntos
Mamíferos , Proteínas , Camundongos , Animais , Proteínas/química , Membrana Celular/metabolismo
20.
Microb Genom ; 9(10)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37850970

RESUMO

Bacterial deficiencies in the DNA repair system can produce mutator strains that promote adaptive microevolution. However, the role of mutator strains in marine Pseudoalteromonas, capable of generating various gain-of-function genetic variants within biofilms, remains largely unknown. In this study, inactivation of mutS in Pseudoalteromonas lipolytica conferred an approximately 100-fold increased resistance to various antibiotics, including ciprofloxacin, rifampicin and aminoglycoside. Furthermore, the mutator of P. lipolytica generated variants that displayed enhanced biofilm formation but reduced swimming motility, indicating a high phenotypic diversity within the ΔmutS population. Additionally, we observed a significant production rate of approximately 50 % for the translucent variants, which play important roles in biofilm formation, when the ΔmutS strain was cultured on agar plates or under shaking conditions. Using whole-genome deep-sequencing combined with genetic manipulation, we demonstrated that point mutations in AT00_17115 within the capsular biosynthesis cluster were responsible for the generation of translucent variants in the ΔmutS subpopulation, while mutations in flagellar genes fliI and flgP led to a decrease in swimming motility. Collectively, this study reveals a specific mutator-driven evolution in P. lipolytica, characterized by substantial genetic and phenotypic diversification, thereby offering a reservoir of genetic attributes associated with microbial fitness.


Assuntos
Pseudoalteromonas , Pseudoalteromonas/genética , Mutação , Biofilmes , Antibacterianos
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